CN102357084A - Enalapril maleate tablet composition and its preparation and use - Google Patents
Enalapril maleate tablet composition and its preparation and use Download PDFInfo
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- CN102357084A CN102357084A CN2011103060439A CN201110306043A CN102357084A CN 102357084 A CN102357084 A CN 102357084A CN 2011103060439 A CN2011103060439 A CN 2011103060439A CN 201110306043 A CN201110306043 A CN 201110306043A CN 102357084 A CN102357084 A CN 102357084A
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- enalapril maleate
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Abstract
The invention relates to the field of hypertension treatment medicinal preparations, and provides an enalapril maleate tablet composition. The enalapril maleate tablet composition comprises enalapril maleate as an active component, one or more organic acids and auxiliary materials. The enalapril maleate tablet composition is characterized in that the one or more organic acids selected from malic acid, tartaric acid and taurine. The enalapril maleate tablet composition improves greatly enalapril maleate tablet storage stability, guarantees medical efficacy and reduces toxicity.
Description
Technical field
The present invention relates to a kind of tablet composition of enalapril maleate, relate in particular to a kind of tablet composition, its preparation method and application in preparation hypertensive medicine of treatment or preparation thereof with enalapril maleate of good storage stability.
Background technology
Enalapril maleate belongs to angiotensin-convertion enzyme inhibitor, is clinical hypertension therapeutic medicine commonly used, and tablet is its application dosage form the most widely.
The chemical stability of enalapril maleate itself is better; But it is because bad with the compatibility of partial supplementary material such as magnesium stearate, microcrystalline Cellulose etc.; There is certain problem in the chemical stability of its tablet, in storage process, usually is degraded into enalaprilat and enalapril diketone.
For solving the storage stability of enalapril maleate tablet, there have been a plurality of patents to deliver.United States Patent (USP) 5,562,921 have reported that the adding sodium bicarbonate uses zinc stearate place of magnesium stearate magnesium as lubricant as stabilizing agent simultaneously in prescription.WO 98/26765 points out in prescription, to add a certain proportion of maleic acid with WO 01/19348 and can be used as stabilizing agent.WO00/66226 claims to add desiccant also can improve the stability of enalapril maleate in tablet.But generally speaking, only have maleic acid to select in the prior art, its range of choice and using value all are very limited; Because different its physical property of organic acid and chemical property all is not quite similar, the occasion that is suitable for is also different, thus be necessary further to study the application of organic acid in stablizing the enalapril maleate tablet formulation, to expand its range of application.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art; A kind of tablet composition, its preparation method and application in preparation hypertensive medicine of treatment or preparation thereof with enalapril maleate of good storage stability is provided; The storage stability of enalapril maleate tablet is greatly improved; Thereby guarantee drug effect, reduce toxicity.
First aspect present invention provides a kind of tablet composition of enalapril maleate, and said compositions contains as the enalapril maleate of active component and medicine stabilizing agent.
Preferably, said medicine stabilizing agent comprises organic acid and adjuvant.
Preferred, said organic acid is selected from one or more the mixture in malic acid, tartaric acid, the taurine.
Further preferred, (molecular weight: mol ratio 492.52) is 0.1～13 for said organic acid and enalapril maleate.
Preferably, the mass ratio of said adjuvant and enalapril maleate is 7-10.
Further preferred, said adjuvant comprises filler, disintegrating agent, binding agent and lubricant.
Further preferred, said filler is selected from one or more the mixture in starch, microcrystalline Cellulose, lactose, pregelatinized Starch, dextrin, the Icing Sugar.
Further preferred, said disintegrating agent is selected from one or more the mixture in low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, the starch.
Further preferred, said binding agent is selected from one or more the mixture in hydroxypropyl emthylcellulose, starch, sucrose, polyvidone, the methylcellulose.
Further preferred, said lubricant is selected from one or more the mixture in magnesium stearate, micropowder silica gel, Pulvis Talci, the Polyethylene Glycol.
Second aspect present invention provides the method for preparing of the tablet composition of said enalapril maleate; Said method for preparing is a wet granule compression tablet, comprises the steps, raw material is mixed with other adjuvants except that lubricant, binding agent; Add binding agent system soft material then; The refabrication granule, dry back granulate, tabletting after the adding mix lubricant.
With respect to the different organic acid among the present invention, when the preparation tablet, can select different hybrid modes, can pass through direct and other raw materials mix of powder, also can the solution form add.
Third aspect present invention provides the application of tablet composition in preparation hypertensive medicine of treatment or preparation of said enalapril maleate.
Be the storage stability of the tablet composition of confirming said enalapril maleate, the inventor has confirmed a kind of medicine stability research method.The inventor finds according to said method research back; The prepared tablet of the tablet composition of enalapril maleate provided by the invention; The storage stability of its enalapril maleate composition has had large increase; 60 degrees centigrade of down heating after 10 days, its undegradable enalapril maleate still remains on original more than 99%.
The specific embodiment
The present invention has adopted a kind of medicine stability research method to measure the stability of enalapril maleate composition in the enalapril maleate tablet:
Place 60 ℃ of heating after 10 days the medicinal tablet that makes; Before will heating respectively with heating after tablet grind, the gained fine powder disperses and ultrasonic 5 minutes with HPLC mobile phase, leaves standstill behind the standardize solution 30 minutes; Get supernatant; Filter with the organic filter of 0.45um, discard filtrating just, collect subsequent filtrate as sample HPLC sample introduction.Prepare the enalapril maleate reference substance solution of a series of variable concentrations simultaneously with mobile phase, the HPLC sample introduction is set up standard curve.Calculate the content of heating front and back enalapril maleate in tablet respectively according to standard curve, according to the heating back enalapril maleate percent retention preceding, the relatively storage stability of prescription than heating.
The HPLC condition: C18 chromatographic column, mobile phase are 10mmol/l pH2.2 phosphate buffer: acetonitrile=75: 25, detect wavelength 215nm, 50 ℃ of column temperatures, flow velocity 1.2ml/min.The compound method of 10mmol/l pH2.2 potassium dihydrogen phosphate wherein: take by weighing the 1.36g potassium dihydrogen phosphate and be dissolved in the 1000ml ultra-pure water, regulate pH to 2.2 with phosphoric acid and promptly get.
Further set forth the present invention below in conjunction with embodiment.Should be understood that embodiment only is used to explain the present invention, and unrestricted scope of the present invention.
Embodiment 1
Prepare tablet by following prescription:
Enalapril maleate 1000g
Tartaric acid 1000g
Lactose 7000g
Low-substituted hydroxypropyl cellulose 1500g
Magnesium stearate 50g
5% starch slurry (mass volume ratio g/ml) 1300g
Process 100,000
Method for preparing: at first prepare 5% starch slurry, then enalapril maleate, tartaric acid, lactose, low-substituted hydroxypropyl cellulose are pressed the recipe quantity mix homogeneously, add recipe quantity 5% starch slurry and process soft material; Cross 20 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds the recipe quantity magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Embodiment 2
Prepare tablet by following prescription:
Enalapril maleate 1000g
Malic acid 100g
Lactose 3000g
Microcrystalline Cellulose 4500g
Cross-linking sodium carboxymethyl cellulose 1000g
Magnesium stearate 50g
5% hydroxypropyl emthylcellulose aqueous solution (HPMC) (mass volume ratio g/ml) 1500ml
Process 100,000
Method for preparing: at first prepare the 5%HPMC aqueous solution, then enalapril maleate, malic acid, lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose are pressed the recipe quantity mix homogeneously, add recipe quantity 5%HPMC aqueous solution and process soft material; Cross 20 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds the recipe quantity magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Embodiment 3
Prepare tablet by following prescription:
Enalapril maleate 1000g
Malic acid 300g
Starch 5000g
Dextrin 2500g
Carboxymethyl starch sodium 500g
Pulvis Talci 300g
Micropowder silica gel 50g
10% polyvidone aqueous solution (mass volume ratio g/ml) 1100ml
Process 100,000
Method for preparing: at first prepare 10% water povidone solution, then enalapril maleate, malic acid, starch, dextrin, carboxymethyl starch sodium are pressed the recipe quantity mix homogeneously, add recipe quantity 10% polyvidone aqueous solution and process soft material; Cross 20 mesh sieve system granules; 50 ℃ of dryings of fluid bed, the control residual moisture adds recipe quantity Pulvis Talci and micropowder silica gel below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Embodiment 4
Prepare tablet by following prescription:
Enalapril maleate 1000g
Taurine 5000g
Lactose 7000g
Dried starch 1500g
Magnesium stearate 50g
5% methylated cellulose aqueous solution (mass volume ratio g/ml) 1100ml
Process 100,000
Method for preparing: at first prepare 5% methylated cellulose aqueous solution, then enalapril maleate, taurine, lactose are pressed the recipe quantity mix homogeneously, add recipe quantity 5% methylated cellulose aqueous solution and process soft material; Cross 20 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds recipe quantity dried starch and magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Embodiment 5
Prepare tablet by following prescription:
Enalapril maleate 1000g
Taurine 1000g
Microcrystalline Cellulose 7000g
Polyvinylpolypyrrolidone 750g
PEG4000?500g
20%PEG4000 aqueous solution (mass volume ratio g/ml) 1600ml
Process 100,000
Method for preparing: at first prepare the 20%PEG4000 aqueous solution, then enalapril maleate, taurine, microcrystalline Cellulose, polyvinylpolypyrrolidone are pressed the recipe quantity mix homogeneously, add recipe quantity 20%PEG4000 aqueous solution and process soft material; Cross 24 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds recipe quantity PEG4000 below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Embodiment 6
Prepare tablet by following prescription:
Enalapril maleate 1000g
Tartaric acid 3000g
Pregelatinized Starch 3000g
Microcrystalline Cellulose 3000g
Sucrose 1000g
Polyvinylpolypyrrolidone 450g
Magnesium stearate 100g
5% starch slurry (mass volume ratio g/ml) 1000g
Process 100,000
Method for preparing: at first prepare 5% starch slurry, then enalapril maleate, tartaric acid, microcrystalline Cellulose, sucrose, pregelatinized Starch, polyvinylpolypyrrolidone are pressed the recipe quantity mix homogeneously, add recipe quantity 5% starch slurry and process soft material; Cross 24 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds the recipe quantity magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content remains on more than 99% after 10 days.
Comparative Examples 1
Prepare tablet by following prescription:
Enalapril maleate 1000g
Benzoic acid 1000g
Lactose 7000g
Low-substituted hydroxypropyl cellulose 1500g
Magnesium stearate 50g
5% starch slurry (mass volume ratio g/ml) 1300g
Process 100,000
Method for preparing: at first prepare 5% starch slurry, then enalapril maleate, benzoic acid, lactose, low-substituted hydroxypropyl cellulose are pressed the recipe quantity mix homogeneously, add the recipe quantity starch slurry and process soft material; Cross 20 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds the recipe quantity magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content is lower than 95% after 10 days.
Comparative Examples 2
Prepare tablet by following prescription:
Enalapril maleate 1000g
Nicotinic acid 5000g
Lactose 7000g
Dried starch 1500g
Magnesium stearate 50g
5% methylated cellulose aqueous solution (mass volume ratio g/ml) 1100ml
Process 100,000
Method for preparing: at first prepare 5% methylated cellulose aqueous solution, then enalapril maleate, nicotinic acid, lactose are pressed the recipe quantity mix homogeneously, add recipe quantity 5% methylated cellulose aqueous solution and process soft material; Cross 20 mesh sieve system granules; 60 ℃ of oven dry of baking oven, the control residual moisture adds recipe quantity dried starch and magnesium stearate below 3%; Mixing, tabletting.
Detecting the gained result through said medicine stability research method is: with compare before the heating, 60 ℃ are heated that enalapril maleate content is lower than 90% after 10 days.
Claims (10)
1. the tablet composition of an enalapril maleate; Said compositions contains as the enalapril maleate of active component and organic acid and adjuvant; It is characterized in that said organic acid is selected from one or more the mixture in malic acid, tartaric acid, the taurine.
2. the tablet composition of enalapril maleate as claimed in claim 1 is characterized in that, the mol ratio of said organic acid and enalapril maleate is 0.1～13.
3. the tablet composition of enalapril maleate as claimed in claim 1 is characterized in that, the mass ratio of said adjuvant and enalapril maleate is 7-10.
4. like the tablet composition of the arbitrary described enalapril maleate of claim 1-3, it is characterized in that said adjuvant comprises filler, disintegrating agent, binding agent and lubricant.
5. the tablet composition of enalapril maleate as claimed in claim 4 is characterized in that, said filler is selected from one or more the mixture in starch, microcrystalline Cellulose, lactose, pregelatinized Starch, dextrin, the Icing Sugar.
6. the tablet composition of enalapril maleate as claimed in claim 4; It is characterized in that said disintegrating agent is selected from one or more the mixture in low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, the starch.
7. the tablet composition of enalapril maleate as claimed in claim 4 is characterized in that, said binding agent is selected from one or more the mixture in hydroxypropyl emthylcellulose, starch, sucrose, polyvidone, the methylcellulose.
8. the tablet composition of enalapril maleate as claimed in claim 4 is characterized in that, said lubricant is selected from one or more the mixture in magnesium stearate, micropowder silica gel, Pulvis Talci, the Polyethylene Glycol.
9. like the method for preparing of the tablet composition of the arbitrary described enalapril maleate of claim 1-8, said method for preparing is a wet granule compression tablet.
10. like the purposes of the tablet composition of the arbitrary described enalapril maleate of claim 1-8, it is characterized in that the application of the tablet composition of said enalapril maleate in preparation hypertensive medicine of treatment or preparation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110306043.9A CN102357084B (en) | 2011-10-11 | 2011-10-11 | Enalapril maleate tablet composition and its preparation and use |
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| CN201110306043.9A CN102357084B (en) | 2011-10-11 | 2011-10-11 | Enalapril maleate tablet composition and its preparation and use |
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| CN102357084A true CN102357084A (en) | 2012-02-22 |
| CN102357084B CN102357084B (en) | 2014-02-26 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105125514A (en) * | 2015-10-12 | 2015-12-09 | 石药集团欧意药业有限公司 | Stable enalapril maleate capsules and preparation method thereof |
| CN107007838A (en) * | 2016-09-30 | 2017-08-04 | 南京优科制药有限公司 | A kind of pharmaceutical composition containing enalapril maleate, folic acid and sour stabilizer |
| CN110917151A (en) * | 2018-09-20 | 2020-03-27 | 杨敏 | Enalapril maleate tablet composition and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041103A (en) * | 1987-04-28 | 1990-04-11 | E·R·斯奎布父子公司 | Globule shape new pharmaceutical composition and formation method |
| WO1998026765A1 (en) * | 1996-12-18 | 1998-06-25 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Stabilized pharmaceutical compositions and process for the preparation thereof |
| CN1518461A (en) * | 2001-06-14 | 2004-08-04 | 大V制药株式会社 | Medicinal compositions |
| CN1822820A (en) * | 2003-07-28 | 2006-08-23 | 雷迪实验室有限公司 | Treatment and prevention of cardiovascular events |
| CN101721383A (en) * | 2009-11-19 | 2010-06-09 | 江苏鹏鹞药业有限公司 | Enalapril maleate tablet and preparation method thereof |
| CN101836982A (en) * | 2010-05-27 | 2010-09-22 | 北京德众万全药物技术开发有限公司 | Medicinal composition for curing hypertension |
-
2011
- 2011-10-11 CN CN201110306043.9A patent/CN102357084B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041103A (en) * | 1987-04-28 | 1990-04-11 | E·R·斯奎布父子公司 | Globule shape new pharmaceutical composition and formation method |
| WO1998026765A1 (en) * | 1996-12-18 | 1998-06-25 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Stabilized pharmaceutical compositions and process for the preparation thereof |
| CN1518461A (en) * | 2001-06-14 | 2004-08-04 | 大V制药株式会社 | Medicinal compositions |
| CN1822820A (en) * | 2003-07-28 | 2006-08-23 | 雷迪实验室有限公司 | Treatment and prevention of cardiovascular events |
| CN101721383A (en) * | 2009-11-19 | 2010-06-09 | 江苏鹏鹞药业有限公司 | Enalapril maleate tablet and preparation method thereof |
| CN101836982A (en) * | 2010-05-27 | 2010-09-22 | 北京德众万全药物技术开发有限公司 | Medicinal composition for curing hypertension |
Non-Patent Citations (1)
| Title |
|---|
| 周新腾，等: "马来酸依那普利制剂稳定性研究进展", 《首都医药》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105125514A (en) * | 2015-10-12 | 2015-12-09 | 石药集团欧意药业有限公司 | Stable enalapril maleate capsules and preparation method thereof |
| CN107007838A (en) * | 2016-09-30 | 2017-08-04 | 南京优科制药有限公司 | A kind of pharmaceutical composition containing enalapril maleate, folic acid and sour stabilizer |
| CN110917151A (en) * | 2018-09-20 | 2020-03-27 | 杨敏 | Enalapril maleate tablet composition and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102357084B (en) | 2014-02-26 |
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